The proposed studies are a continuation of the principal investigator's research interests in 5 areas: 1. the peripheral metabolism of the thyroid hormones especially the physiologic role of the human and rodent placenta in modulating the transplacental passage of the thyroid hormones in vivo and the nutritional control of TBG generation and the deiodination of the iodothyronines in the lean and genetically obese Zucker rat; 2. the use of 125I-Triac as a probe to quantitate the T3 nuclear receptor in rat tissues and human peripheral lymphocytes under a variety of abnormal thyroid and non-thyroid states; 3. the interrelationship between two neuropeptides (neurotensin (NT) and substance P (SP) and a recently described potent endogenous opioid peptide (dermorphin) with TRH and the thyroid hormones in the control of TSH secretion in vivo by hypothalamic microinjections of NT, SP and dermorphin and in vitro using pituitary and hypothalamic fragments; 4. the effect of excess iodide on thyroid function in patients receiving amiodarone and lithium and in the spontaneous diabetic BB/W rat who develops autoimmune lymphocytic thyroiditis (LT; 5. attempts will be made to enhance or attenuate LT in the BB/W rat with transferred or spontaneous diabetes mellitus by low or high iodine intake and the administration of methimazole which appears to be an immunosuppressant of the thyroid lymphocyte. These efforts should further our understanding of the regulation of adult and fetal thyroid function under normal and pathological conditions and are directly related to previous and present activities in our laboratory.